Regional Stasis Blood in Dysfunctional Left Ventricle ...

Regional Stasis of Blood in the Dysfunctional
Left Ventricle: Echocardiographic Detection
and Differentiation from Early Thrombosis

FRANK L. MIKELL, M.D., RICHARD W. AsINGER, M.D., K. JOSEPH ELSPERGER. CCPT,
W. ROBERT ANDERSON, M.D., AND MORRISON HODGES, M.D.

SUMMARY In two-dimensional echocardiographic studies of left ventricular thrombus in patients, an
unusual pattern of dynamic left ventricular intracavitary echoes was identified in some hearts with severe
apical dysfunction. These intracavitary echoes were noted in the apical region and were distinct from left
ventricular thrombi. Certain features of the intracavitary echoes suggested that they were generated by
regional stasis of blood. To study this phenomenon, echocardiography was performed in 1I dogs with
experimental anteroapical infarction and associated left ventricular thrombus and in six dogs with infarc-
tion but no thrombus. The dynamic intracavitary echo pattern suggesting blood stasis was identified in the
ischemic apex in dogs of both groups. These echoes had characteristics suggesting a fluid or semifluid state
and could be distinguished from thrombi. In real time, the echoes moved in a slow, circular fashion at the
apex and lacked well-defined borders; their configuration and acoustic intensity changed over short periods
of time, and they could be rapidly altered bv ectopic or mechanical contraction of the heart and by
dopamine infusion. Postmortem examination showed that liquid blood produced the echoes.

Additional studies demonstrated the echogenicitv of static blood. Echocardiography of dog hearts with
KCI-induced mechanical-asystole showed the rapid development of diffuse echogenicity of the intraventricu-
lar rontents; in vitro studies confirmed the echogenicity of static blood.

These observations indicate that a spectrum of echocardiographic features characterizes ventricular
blood under various conditions of flow and with frank thrombosis. The ability of echocardiographv to detect
in vivo stasis of blood in the left ventricle and to distinguish this from thrombosis has important clinical and
investigational implications.

IN 1975, using M-mode echocardiography, Feigen- Materials and Methods
baum described accumulations of intracavitary echoes
Definitions
next to dyskinetic segments of the left ventricular wall
in patients with coronary artery disease.' He thought The following terms are defined as they are used in
these echoes were generated by sluggish blood flow in the manuscript:
the area of regional ventricular dysfunction. More re-
cently, Sigel et al. demonstrated the echogenicity of Dy,namic intracavitarv, echoes the pattern of ech-
static blood in both in vitro experiments and in the
totally occluded canine vena cava. In studies of left oes in the ventricular apex that suggests regional stasis
ventricular thrombus using two-dimensional echocar- of blood.
diography,- 4 we noted dynamic intracavitary echoes
in the apex of some patients with severe apical wall Blood stasis - slowing of blood flow velocity from
motion abnormalities; these echoes were distinct from normal conditions.
thrombus and had characteristics suggesting that their
source was blood stasis. In studies of experimental left Static blood - blood with complete cessation of
ventricular thrombosis in dogs5 we also found that flow.
these dynamic-intracavitary echoes were distinct from
thrombi. Echodensity - a qualitative term describing the rel-
ative acoustic intensity of echoes produced by a sub-
In this report, we present the characteristics of these stance, i.e., the greater the echodensity of an echo
intracavitary echoes in man and in dogs and the results target the more intense and visible the echoes produced
of animal studies. for a given ultrasonic gain and reject setting.

From the Cardiology Sections of Departments of Medicine and Pa- Patient Studies
thology, Hennepin County Medical Center and the University of Minne-
sota. Minneapolis. Minnesota. We reviewed approximately 2800 consecutive two-

Presented in part at the Annual Meeting of the American Colleze of dimensional echocardiograms performed over a 2½/2-
Cardiology, March 1981. San Francisco. California.
year period. Forty-nine patients had echocardiograms
Supported in part by grant 0685-5788 from the American Heart Asso- either diagnostic or highly suggestive of left ventricu-
ciation. Minnesota Affiliate. lar thrombi by previously reported criteria.' The pa-
tients were studied with a mechanical sector scanner
Address for correspondence: Frank L. Mikell. M.D.. Cardiovascular (Advanced Technologies Laboratory, Mark III) and a
Clinic, St. John's Hospital, 800 East Carpenter. Springfield. Illinois 3-MHz transducer. A systematic examination was per-
62769. formed in parasternal, apical and subcostal acoustic
views with varying sector orientations.6 The apical
Received December 28, 198 1: revision accepted February 25. 1982. precordial view was the most useful for detecting both
Circulation 66, No. 4, 1982. thrombus and the echocardiographic patterns associat-
ed with blood stasis. For the apical views, patients
were examined in the left lateral decubitus position

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756 CIRCULATION VoL 66. No 4. OcFr()BiR 1982

with the head slightly elevated and the transducer docardial injury and provide a nidus for thrombus for-
placed at the point of maximal impulse. Shallow depth mation. The dogs were allowed to stabilize, and serial
settings of 7 and 9 cm for the apical views were par- echocardiographic images were obtained at 20-30-
ticularly helpful for detailed imaging and for maintain- minute intervals over the next 4-8 hours. These 11
ing good near-field resolution. In four patients in dogs were studied echocardiographically until a defi-
whom the echocardiographer suspected a pattern of nite mural thrombus was detected and its size remained
dynamic intracavitary echoes on the routine examina- stable for 1-2 hours.
tion, a 5-MHz transducer was applied to the apex with
shallow depth settings to enhance near-field resolu- In the remaining six dogs (group 2), coronary liga
tion. In three such patients, images were obtained with tion was performed as in group 1, but sodium ricino-
both the mechanical sector scanner and a phased-array leate was not injected. Solandt et al. reported that
ultrasonograph (Varian Instruments, Varian-3000). thrombus does not usually acutely develop in this situ-
which has a 2.5-MHz transducer. ation. Ischemic wall motion abnormalities were docu-
mented echocardiographically in these dogs. They
To obtain information on the incidence of the dy- were then followed with the serial echocardiographic
namic intracavitary echo pattern in patients with severe protocol used in group 1.
apical wall motion abnormalities, we reviewed 52 con-
secutive patients with electrocardiographic anterior In Viv!o Exvper-imental Interv!entions and Studies
myocardial infarction prospectively studied with two- of Static: Ventricular Blood
dimensional echocardiography. These patients were
originally studied to determine the incidence of left Several interventions were performed in the group 2
ventricular thrombosis in acute myocardial infarction.; dogs to assess their effect on the dynamic intracavitary
Myocardial infarction was defined by typical clinical echocardiographic patterns. In three dogs., dopaminne
history; evolutionary electrocardiographic changes, was infused. Pulmonary arterial, aortic and left ven-
including the development of new Q waves; and typi- tricular pressures were measured and cardiac output
cal serial cardiac enzyme patterns of total CK, the MB was determined in triplicate by the indocyanine green
fraction of CK, and lactic dehydrogenase. No patient dye technique using a cardiac output computer (Model
had historical or electrocardiographic evidence of prior RLD, Lexington Instruments). Hemodynamic varia-
myocardial infarction. Two-dimensional echocardiog- bles were measured with simultaneous echocardio-
raphy was performed within 72 hours of admission and graphic images before and during i.v. dopamine
serially during hospitalization. In each patient, apical administration. 7.5 jtg/kg/min, after the coronary
wall motion was analyzed and classified as normal,
hypokinetic, akinetic or dyskinetic.4 ligation.

Experimental Animal Studies In three dogs, 5-10-ml boluses of normal saline
were injected into the left ventricle or left atrium to
Animnal Preparation obtain echocardiographic contrast ventriculograms .8
Saline was injected before and after coronary ligation.
Studies were performed in 17 mongrel dogs that and echocardiograms were obtained simultaneously.
weighed 17-30 kg. The dogs were anesthetized with In addition. external manual compression of the in
i.v. pentobarbital, 20-25 mg/kg, supplemented as re- vivo hearts was also performed during echocardiog-
quired, and ventilated with a positive-pressure respira- raphy in several group 2 dogs for one or two contrac-
tor with supplemental oxygen. The heart rate was mon- tions so the effects of this maneuver on the intracavi-
itored by ECG. The heart was exposed through a tary echoes could be viewed. Each tape was also
midline sternotomy and suspended in a pericardial reviewed for the effects of spontaneous ventricular ec-
sling. Baseline two-dimensional echocardiograms topic contractions on the echocardiographic patterns.
were then obtained. After i.v. lidocaine, 2 mg/kg, was
given, the middle portion of the left anterior descend- After the last in vivo echocardiographic imaging,
ing coronary artery was ligated. Additional epicardial
coronary arteries supplying the apex were identified dogs from both groups were injected in a peripheral
and ligated near the apex. This method of ligation vein or the descending aorta with a concentrated potas-
produces transmural infarction and generates an echo- sium chloride solution. Continuous two-dimensional
cardiographic pattern of abnormal apical wall motion echocardiographic imaging was then performed in the
majority of dogs until mechanical asystole had been
similar to that in patients with anterior myocardial in- present for several minutes. Several of the asystolic
farction.4 The dogs were allowed to stabilize for 15-20 hearts were externally manually compressed while
minutes and echocardiograms were obtained to docu- echocardiographic imaging was continued. The hearts
ment the wall motion abnormality induced by coronary were then removed. The aorta was clamped and the
ligation. base of the heart and pulmonary veins tightly grasped
and pulled ventrally to ensure that the left ventricle was
In 11 of the 17 dogs (group 1),, left ventricular inural in a dependent position during dissection and that ven-
thrombi were generated by injecting several 0.25-ml tricular contents did not escape during removal of the
volumes of 5% sodium ricinoleate into the apical sub- heart. The left ventricles were opened for gross inspec-
endocardium. 7 Sodium ricinoleate is a free fatty acid tion and the liquid contents were strained through
small-pore cloths. Thrombi were measured as pre-
ester that acts as a sclerosing agent to produce suben- viously described.> The hearts and thrombi were then

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ECHO DETECTION OF BLOOD STASIS/Mikell ct .7l. 75S7

fixed in formalin and areas of the thrombi were sec- Platelet aggregation was confirmed by visual inspec-
tion and by aggregometry (Bio-Data Corp., model
tioned for histologic examination. PAP-3). Echocardiographic imaging was performed in
each specimen with and without mechanical agitation
Echocardiographv of the latex tube over the range of gain and reject
settings.
Echocardiographic imaging in the dogs was per-
formed with the mechanical sector scanner (Advanced Results

Technologies Laboratory, Mark III). The transducer Echocardiographic Pattern of Blood Stasis in Patients

was placed lightly on the exposed surface of the heart; Nine patients had definite evidence of dynamic in-
aquasonic gel was used as a conduction medium. tracavitary echoes suggesting blood stasis in the left
Echocardiographic views were obtained that showed
the entire left ventricle and the apex in particular. ventricle (table 1). These echoes were seen only in the
These views included an anteromedial position at the
mid-heart level with the sector orientation in the long apical region and had features suggesting a fluid or
axis of the heart and the left ventricular apex using semifluid state. The echoes were of variable amplitude
multiple sector orientations in both the long- and short- and density and moved in slow circles in the apical
axis planes of the heart. Although no effort was made region (fig. 1). All nine patients had severe apical wall
to precisely simulate views obtained in patients, these motion abnormalities with either akinesis or dyskinesis
two echocardiographic windows produced images of the ventricular apex. Eight of the nine had a history
similar to those obtained in patients with the paraster- anterior myocardial infarction: four were recent (with-
nal long-axis view and the apical two- and four-cham- in 3 weeks) and four were remote. One patient had
ber and apical short-axis views, respectively. In nine congestive cardiomyopathy. Three patients had clini-
dogs, images were obtained with 3-MHz and 5-MHz cal congestive heart failure requiring therapy; two
transducers for comparison. Only the 5-MHz trans- were taking systemic anticoagulants at the time of
ducer was used in the other dogs. imaging. Seven of the nine had echocardiographic evi-
dence of associated mural thrombus at the apex. The
The echocardiographic studies were interpreted by thrombi were distinct from the dynamic intracavitary
three experienced echocardiographers. In the last 11 echoes in each patient. In one patient without an asso-
dogs including all six in group 2, the tapes were inter- ciated mural thrombus, the effect of sublingual nitro-
preted blindly by an examiner not present in the labora- glycerin on the intracavitary echoes was examined.
tory when the studies were performed. The echocar- After nitroglycerin, the intracavitary echoes changed
diograms were recorded on ½/2- or -1/4-inch videotapes configuration and seemed to coalesce within the cen-
for subsequent review. tral portion of the apex. Over several minutes this
coalescence receded and the echo pattern returned to
In Vitro Studies the baseline state. In two other patients with abdominal
aortic aneurysms (table 1), a similar pattern of echoes
In vitro water bath studies using the same two-di- was noted within the aneurysmal aortic segment. In
mensional mechanical sector scanner were performed both, the echoes of blood stasis were distinct from
to further investigate the genesis of the intracavitary those of mural thrombi in the aneurysm.
echo patterns seen in vivo. Whole blood specimens (6-
8 ml) from a dog and from a human volunteer were Forty-one of the 52 consecutive patients (79%) who
drawn in buffered EDTA solution. The specimens had had their first anterior myocardial infarction had
were transferred into flexible latex tubes, 0.6 cm in apical akinesis or dyskinesis present on at least one
diameter, sealed at one end. The tubes were clamped echocardiogram. Two of these 41 patients (5%) had
and suspended in a water bath, which served as an dynamic intracavitary echoes suggesting blood stasis.
ultrasonic conduction medium. Another tube that con- One of these also had a mural thrombus echocardio-
tained a similar volume of saline was used as a control. graphically. The other patient did not have a mural
The tubes were imaged with the 5-MHz transducer thrombus; subsequent echocardiograms showed that
over the range of gain and reject settings of the echo- the apical wall motion had improved and the dynamic
cardiographic instrument. intracavitary echoes were absent.

Using the same approach, platelet-rich plasma, In the three patients in whom the left ventricle was
platelet-poor plasma and stimulated platelet aggregates studied with both the mechanical sector scanner and
from both species were imaged in a water bath at a the phased-array ultrasonograph, the intracavitary ech-
temperature of 370 C. Platelet-rich plasma was pre- oes were seen with both instruments. The echoes were
pared at room temperature by collecting blood in plas- more distinct on echocardiograms obtained with the
tic tubes containing 3.8% sodium citrate and centrifug- mechanical sector scanner.
ing at room temperature at 800-1000 rpm for 10
minutes. The plasma was then separated and intro- Animal Experiments
duced into the latex tube. Platelet-poor plasma was
similarly obtained and centrifuged at 3000 rpm for 10 Left Ventricular Apical Wall Motion Abnormalities
minutes. Platelet aggregates were generated in the la-
tex tube by injecting 1 ml of adenosine diphosphate, 10 Coronary ligation resulted in echocardiographically
ptg/ml (Sigma #AO127) into the sealed latex tubes distinct apical wall motion abnormalities; each dog had
containing human or canine platelet-rich plasma. akinesis or dyskinesis during systole (table 2). The

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758S CIRCULAT'ION 7Vo-1 66. No 4. 0(i o(i)Bin:R 198.2

TABL. 1. Paticnt.s ii it/I LcliortoiZi/ in of Bloodhri vStoIsis

Age Location Apical wall Associated
ot' echoes Motion thi-omlbtis
Pt (years) Scx Clinical settin-,

1 35 NI Rccent AMI Apex D-skinetic Ycs

2 31 -F Recent AMI Apex D\-skiietic Yes
3 58 M Reimiote ANI Apcx Akiinctic
Yes

4 63 M Rciotc AMI Apex Dxskinetic Yes
Dvskinctic Ycs
5 57 M Recent AMI Apex

6 67 M Rciemote AMI Apex Dvskineti Ye

7 62 M Remiote AN!! Apcx Dx)skinetic No

8 68 F (CCM Apcx Akinctic YTc

9 5 6 M Recent ANI! Apex Akiinctic No
Ycs
3() 772 M Aortic afCUISI11m AbhcomeInc-

1! 68 MI Aortic aneurysm Abdomnci Yes

Abbreviations: AM! anterior mn ocardi.al intarction. CCM = conmestive cardiomyopath.

pattern of regional dysfunction in these dogs was quali- tions were of such acoustic intensity that no difference
tatively similar to that in the majority of patients with was noted between the transducers.'
isolated acute anterior infarction reported by Asinger
et al.4 Iltracai itarv Echocirdiogr-aphic Pattet-ns

Echocardiographic Feature.s of EAp:erimienital Acictt of Regional Blood Sta.sis
Thrombosis and Histopathologic Correlates
In seven of the 1 I dogs with left ventricular thrombi.
In all dogs in group 1, left ventricular mural thrombi an intracavitary pattern of echoes identical to that de-
attached to the apical endocardium were imaged echo- scribed above in patients was seen in the left ventricle
cardiographically (fig. 2). The echocardiographic ancd (table 2). The ultrasonic pattern was characterized by
histologic features of the thrombi have been reported in low-amplitude, variable-density echoes that moved in
detail.' The mural thrombi were located at the apex. At slow circles within the dysfunctional apex. Echocar-
autopsy. they were 0.6 x 0.5 to 2.1 x 2.0 cm. The diographically, this pattern was distinct from both the
echocardiograms showed that these endocardial mural endocardial and tail portions of thrombi. At postmor-
thrombi had no significant intracavitary motion. In six tern examinations, only liquid blood was found in the
of the 11 dogs, we found a portion of thrombus that ventricle to explain the echoes.
was distinct from the endocardial portion. This second
portion of thrombus was a tail-shaped mass that was In the six dogs that did not receive a ricinoleate
attached to the endocardial thrombus and extended into injection, the intracavitary echo pattern was detected
the left ventricle (fig. 2). The tails moved during the in the dysfunctional apex in the absence of echocardio-
cardiac cycle and had well-defined, consistent borders graphic evidence of mural thromiibus (table 2, fig. IC).
echocardiographically. These thrombi were less As in patients (fig. I A), the echoes in the dogs showed
acoustically intense than the endocardial thrombi. but variable acoustic intensity and a slow. circular move-
had homogeneous acoustic density. ment within the apical area. The most acoustically
intense intracavitary echoes produced a pattern that
Autopsy examination confirmed the presence of simulated an endocardial thrombus if viewed for only
thrombus in all 1 1 dogs. Histologicaly, the endocardial one or two cardiac cycles (fig. 3A). The echoes occa-
thrombi were characterized by typical platelet lamellac sionally formed a vortex that simulated the red throm-
bordered by leukocytes (lines of Zahn) interspersed bus tails seen in some group 1 dogs. Real-time images
among fragmented erythrocytes. In the dogs that had over several cardiac cycles. however. showed differ-
two distinct portions of thrombus echocardiographical- ences between this intracavitary echo pattern and that
ly, gross examination showed two distinct areas of with thrombosis. In contrast to the echocardiographic
thrombus, In these dogs, a tail-shaped red thrombus picture of frank thrombosis. these intracavitary echo
was attached to the endocardial thrombus and extended patterns lacked features suggesting a mass. The bor-
toward the outflow tract. The red tails differed from the ders of the echoes were evanescent and poorly defined.
endocardial thrombi and showed nonfragmented eryth- and areas within the echoes appeared to coalesce and
rocytes enmeshed in a fine fibrin network, with mini- then disperse over several cardiac cycles. The intra-
mal or no platelet lamellae.5 cavitary echoes had fluid characteristics and resembled
smoke moving slowly through a light beam in a dark-
Both portions of the thrombi were seen by blinded ened room. In each group 2 dog, this echo pattern was
observers reviewing the videotapes recorded during seen within the ventricle in the absence of echocardio-
imaging with both the 3- and the 5-MHz transducer. graphic evidence of mural thrombus. At postmortem
The 5-MHz transducer. however. provided better examnination, only liquid blood that passed through the
near-field resolution and showed the less acoustically cloth filters was present in the ventricle.
intense tail portions more clearly. The endocardial por-
A consistent echocardiographic feature that indicat-

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ECHO DE LEC'I ION OF BLOOD S l ASIS/Mikell et a.l. 759

ed the fluidity of these intracavitary echoes was their sii i-E 2. Anmniiul StVntlies Apical wall Associated
evanescent configuration and variable acoustic den- motion th rombus
sity, similar to that seen in the patient given nitroglyc- Group I Echooenic
erin. Venitricular ectopic beats or external mechanical I blood MLural + tail
contraction of the heart iinmediately altered the shape 2 stasis Mural + tail
and motion of the intracavitary echoes, as did infusion 3 Mural + tail
of dopamine. Figure 3 illustrates this phenomenon. 4 inl vivo Locatioen Mural + tail
This sequence of views was obtained during continu- NMLural + tail
5 N)o Dvskinetic Mural only
ous imaging over several minutes without changing the 6 Yes Apcx Dyskinetic Mural + tail
tranducer gain or reject settings. In figure 3A, a rela- 7 Yes Apex Akinetic
tively dense group of echoes can be seen at the apex. 8 Mural only
The echoes have suflicient acoustic intensity and ho- 9 Yes Apex Dyskinetic
10 No Dyskinetic Mural only
mogeneity to simi1ulate a thrombus. A dopamine infu- Yes Apcx Dyskinctic
sion was then initiated. FigUre 3B obtained a few 11 No) Dvskinetic Mural only
Group 2 Yes Apcx lDyskinetic
No Dyskinetic Mural onlyot
12 Ycs Apex Dyskinctic
13 Ycs Apex Dvskinetic None
14 None
15 Yes Apex D)yskinetic None
16 Yes Apex Dyskinctic None
17 Yes Apex DNyskiioetiL None
None
Yes Apex 1)yskinctic

Yes Apex Akinctic

Yes Apex Dyskinetic

cardiac cycles later after a short run of ventricular
tachycardia, shows a rapid transformation in the con-
figuration of the echoes into a large curl with the tip
movinT circularly. Figure 3C was obtained minutes
later, after the hemodynatmic effects of dopamine on

heart rate and systolic blood pressure had Occutrredl.
-4-1 The echoes have been completely dispersed from the

central apical cavity, and in real time appeared to layer
along the ventricular wall. After the dopamine infusion
was stopped, the pre-dopamine pattern recurred. At
autopsy shortly after this intervention, only liquid
blood was found in the ventricle.

Qualititive Pattern-Ls of Blood FlHto

in the Left Ventricle

In three group 2 dogs, normal saline was injected
into the left atrium or left ventricle before and after
coronary ligation to generate an echocardiographic
contrast medium.i Before coronary ligation, the con-
trast echoes filled the ventricle uniformly and emptied

F RitIRF 1 (A)JSti//-franie el)/ thIt di/)i til rico in
pae/iet 7. Ii/,(itieil t remiiote (itnter-ior InsocatIrlial iifartcion.
Apical dv,ski/iseiA was. seefI in retl-tim/ie itages. The apical
regifo tV/ititisloiS taiiplitatldc vartiable-dens itv iuit/rictaitatir
echoes (arriw) thitit inoi-etl iIn a cs/o irtle iIntt/IlieIrectionl of'tile

rtIrow. (B) Schematic of fthe f/ltl intracavitarY echlioes in fii,ure
IA. (C) Ai eclhocardliogitmi fioimi a /oiog ill tgr/(Jp) 2. As iii
f)tatienits. the a/)v sliowel lski.Sknedc /biugi/iig. ciiitl tiatnic- inl-
IrtctIIrihttI i echoes wverI'e 1pri.esetIfil (arrwortoi'). At tunitops s;v Ii /IitIid
1/othlotiws p/e.se/it i theven/tricle. LV l,left ve/it/icles LA

left tirin/n}.

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760( CIRCULA'I'ION Vot. 66. No 4, 0cnnom:R 1982

Fai(iu ' 2. (A) lo-c/imeiicisiotici/l cchoccodilotrphic still Fi;t RiE 3. (A) E/chocarlcdiogra/phic cipiccil vi/ci front e clog inl
frctnc fioni bcidclog in1 ottgrI 2s/otwi'g c /clft v nirtricular thiroinbus
with/ tl'o distinct /portioiis.. ]lhe endocacd/to 1itoo11 thromnbus (T) gtr)it/) 2 withiou/)t cssociatct t/ i/irotnbits. f/7toe is citi roeim/sf'
i.s attachcec/ttoctli itex idst iott'ticctl/s inItenfl so'. Atuit lied to
ecc/cd/censc /)catttrt of bloodl stcasis (corotws) ctt i/ic' ta/)x. I/oe
1/its is tlic/c'a ' tc/ oftt/rombi/)ts ( llrolt's) to7tt is less i(conslticll//s
ctouslitc/dilslitv ctnlcl shlicpe)f /ictlie choes stidlcateti thronibus,
i.ntense citicl cxten/is inlto telftlventri le. In rectil-titlt' ifncIt(Is,
/)lit inI retil toime, the lnitrc ticts s oft choes o tvec iiit/ci/ iII
1)01/ compi/onients licd tie/I c/cfined borders cIincl oppecrecIcs
c/isstoi't MiicisSes. LV leift entric le Ao ciorict: LA Icfo to1e cipicci/ tOt4i )ii. (B) T/to uticiss of echoes setet in figure 3A swere

cttriitn. (B) Scheomotic offtigire 2. ct/alit/Is tIrconsfornidCc cieft three -beat Nt/b o(f ventricula/r

within a few cardliac cycles. No regional LacumLlulation Itcic/i c(itcdict cis clopconine itfits/ott ticas initititec/. T/its tistcOiti/t
of the contrast echoes was nioted. Alter coronary lia- cilterec/ t/IC ctcotstit ois/e.itv t tcl/1/ic c-otifigtrcn'itio oof /ithc echoes,
tion, contrast echoes entered the dysfunctional apicLiI clltc ci (itt/ c/d pctttcnItIt ciS t1)p1c/itu ced (ctriow). T/i/s vi/it ivaus
area and persisted, while echoes in the basilar por-tioin
o)btclicetcc wit/I t1/e sctiofJ tcrttschtcer pos-itioti ciiic/ gctin-reject
of the ventricle cleared. The contrast echoes confined
to the apical area miioved in aL circle, as did the intra- settiongs icscc bo obtci/n figuitr 3A, t/lt/lioitg/i 1/i depth/ scte/c is'
cavitary echoes (fig. I ). However, the echoes cenerat-
rechucedl. (C') Wit/i /til'I0s oflictinfaheoc inamic efffcetctjotn c/opc-
ed by saline injection had acoustic proper-ties differ-ent
intie, t1ie cipiccil cc/toes sooni in figunres 3A cn/d 3B cire niolt
from those of the intracavitary echoes.
cotp/Cletsy c/ispersfedUrotn t1/i cenlta/l por-tiot c)f /tlie ci-po. InI
Sttcl/ies oni t/ie Echogeieits qoSficatic Bloof
reci/ time,1t/e cc/toes cippecirecl to /taver ci/oitgg1/i sept/l cial/
Figure 4, obtained from a dog in group I illuStrIateS
an echocardiographic phenoinenon seen after KCI in- (carrowt s). After t1/i c/opcnneittii itiflitsol/ Ircis Stoppcc/, tIc pcittecrii
jection. Before KCI injectioni, the echocardtiorams s/howtti in ficurc 3A recttrrec/. Ott/s /ic/tcbi/id c/otoi cis. f'unttic ttle
showed an endocardial thrombus andi dynamaiic intra-
cavitary echoes at the apex (fig. 4A). As the blood ventricl/ cit clUttc)/o.5
pressure deteriorated atter injection of KCIL but before
comnplete mechanical asystole. the intracavitary echoes
at the apex becamne more intense and homogenoLus.
Similar low-density echoes beglan to dlevelop in the

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ECHO DETEC IION OF BLOOD STASIS/Mikell et a!l. 761

FIGjURi' 4. (A) Apical still frame ininiieciliatels befor(e KCU! inl- let-rich plasma from both species produced grossly
visible platelet aggregates, confirmed by aggregom-
jectioln iln a gru)p / clog. A micilil thlr oinibifs (T) is present at the etry. Echocardiographic imaging showed no acoustic
reflectiveness from the platelet aggregates, even when
left ventricular apex. The /bxsilit/ por-tion (ffthe Ieft ventricle the tubes were agitated.

(LV) is ec hol/c enit. RV rig/it ventricle. (B) Ec/zocardio,grcn Discussion

obtaiined .shortlv, aifter KC/-induced mechanica/l asvstole /l)t /)- Our findings show that in vivo regional stasis of
blood in the left ventricle can produce an ultrasonic
Jore cessation of oranizec/ e/ectrica/l actilvitl'. pattern that is distinct from left ventricular thrombosis.
Distinct echocardiographic patterns appear to charac-
basilar portions of the ventricle near the mitral valve. terize intraventricular blood under conditions of nor-
With mechanical asystole, the left and right ventricles mal flow, with severe regional stasis, and with throm-
and atria displayed a homogenous echodensity (fig. bosis. When blood flow is normnal, intracavitary
4B). The mural thrombus remained slightly more in- ventricular blood does not produce a recogniiable
tense than the ventricular contents. External mlanual
contraction of the heart produced an agitated motion of echogenic pattern when imaged with 3-5-MHz ultra-
the diffuse intracavitary echoes, which indicated their sonic transducers; the blood is echolucent, despite the
fluid nature. Opening the heart and straining the con- wide range of intraventricular pressures and flow
tents confirmed that only liquid blood and the endocar- velocities during the cardiac cycle. In the setting of
dial thrombus were present. In dogs without associated severe regional ventricular dysfunction, especially at
mural thrombus, this pattern of diffuse intracavitary the cardiac apex, stasis of intracavitary blood occurs,
echogenicity was present during mechanical asystole, and the acoustic properties of the blood in the area of
and autopsy showed that only liquid blood was present dysfunction may produce a discernible echogenic pat-
in the ventricles. tern. A thrombus in the ventricle is an acoustically
detectable mass with distinctive echocardiographic
In Vitro Water Bath Studies
patterns.
Both human and canine static whole blood were Several lines of evidence indicate that the in vivo
intensely echogenic, whereas control normal saline
was echolucent. Platelet-rich and platelet-poor plasma intracavitary echo patterns seen in patients and in dogs
from humans and canines, however, did not produce are caused by stasis of blood. First, postmortem ex-
detectable echoes in the latex tube system even with amination of the dogs showed only liquid blood to
mechanical agitation and were not different from saline explain the echoes. Second, the intracavitary echoes
controls. Addition of adenosine diphosphate to plate- are seen only in areas of altered blood flow. Both
patients and dogs had severe regional dysfunction of
the ventricular apex, evidenced by akinesis or dyskine-
sis in systole. In dogs, altered blood flow in the dys-
functional apical region could be deduced from the
saline injections after coronary ligation. Postligation
injections demonstrated relative persistence of echo-
genic contrast at the apex and circular motion of the
contrast identical to that of the intracavitary echoes.
Third, the configuration and motion of the intracavi-
tary echoes indicate that their source is a fluid state,
unlike the echocardiographic features of thrombosis.'
These intracavitary echoes show a dynamic variation
in shape, conformation and acoustic density, even
when they are acoustically intense and relatively ho-
mogeneous. Furthermore, alterations in ventricular
contraction produced by ectopic beats, dopamine infu-
sion, or mechanical external contraction lead to rapid
changes in the configuration and density of the echoes.
Last, static blood is echogenic. Normally echolucent
blood becomes strikingly echogenic with the induction
of mechanical asystole before postmortem clot fotrma-
tion. Our in vitro water bath studies and the studies of
Sigel et al.2 also demonstrate the echogenicity of static
blood.

An important finding in this study is the ability of
real-time two-dimensional echocardiography to distin-
guish in vivo intraventricular blood stasis from throm-
bosis. Endocardial left ventricular thrombi have char-

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762) CIRCULATION Vo,- 66, No 4. Oc T)OER 1982

acteristics of a definite mass on two-dimensional regional conformation after ischemia. In a prospec-
tive study of left ventricular thrombus formation after a
echocardiograms, are acoustically distinct from under- first myocardial infarction, apical systolic akinesis or
lying myocardium, and have distinct margins.3.5 Al- dyskinesis was significantly related to left ventricular
though blood stasis without thrombosis may some-
times have sufficient acoustic intensity and uniformity thrombus formation.4 The unique cup-like shape of the
apex and its primary contribution to the long-axis sys-
to simulate a thrombus (fig. 3A), real-time imaging tolic shortening of the heart may contribute to the pre-
disposition of this region to blood stasis during ische-
over several cardiac cycles or after ectopic contrac- mic dysfunction. Thus, blood adjacent to an akinetic,
but nonaneurysmal, inferior wall might demonstrate
tions demonstrates obvious changes in the configura- less derangement of flow during the cardiac cycle be-
tion and acoustic uniformity of these echoes and indi- cause of the influence of a normally contracting ante-
rior free wall or apical segment. In contrast, akinesis of
cates a fluid state. Even the tail-shaped mobile red
thrombi seen in some group I dogs could be distin- the apex produces isolation of the blood in this region.
and other normally contracting proximal ventricular
guished from static blood. These red tails have been walls cannot affect the blood in this area as profoundly.

described as components of intraarterial thrombi' and Our findings support the hypothesis that the more

may represent rapid propagation of thrombus in an area severe the degree of blood stasis present, the more
of low blood flow.10 Although less acoustically intense
than endocardial-based thrombi, the red thrombi had pronounced the changes that lead to blood echogenic-
distinct margins (fig. 2A) that remained intact over ity; however, intraventricular stasis of blood cannot be

long periods of time and after ectopic contractions. quantitated. The degree of left ventricular dysfunction
caused by general anesthesia. for example, did not lead
The changes that occur in blood in areas of stasis and
to echogenicity of the intracavitary blood. Ischemical-
cause it to become echogenic are unclear. In vitro ly induced severe regional dysfunction, however, pro-
duced regional echogenicity. while complete mechani-
evidence suggests that certain components of static
blood are echogenic while others are not. Sigel et al.' cal asystole led to a diffuse echogenicity of the
demonstrated that whole blood, but not plasma and ventricular contents. There may well be a variable and
serum. is echogenic in vitro. Erythrocvtes suspended
nonlinear relationship between the degree of blood
in plasma, but not in serum or in saline, produce visi-
ble echoes. Our in vitro experiments support these stasis and blood echogenicitv. Different blood types,
findings and provide evidence that platelet aggregates
are probably not the source of blood echogenicity. erythrocyte concentrations. or species might have

Neither platelet-rich plasma nor epinephrine-induced different 'thresholds' of stasis at which blood be-

platelet aggregates produced echoes in a static state oI- comes echogenic. Investigation into this area will re-

after mechanical agitation that could be detected with a quire development of models or methods for quantitat-

medium-frequency (5-MHz) transducer. The echo- ing blood stasis in the dysfunctional ventricle, where
flow patterns are more complex than in peripheral
genicity of blood components mav also depend on vessels.
factors related to blood flow, including rheolocic and
biochemical properties. and changes in the phvsical Technical aspects of the echocarciographic exami-
alignment of potentially echogenic blood components
in the area of blood stasis. Sigrel et al.' postulated that nation and the ultrasonic frequency are also important
physical layering of static blood might be an important considerations in a study of the acoustic properties of
consideration in its echogenicity. Our observations blood. These factors, as well as the biologic tactors
support the plausibility of this hypothesis in the in vivo noted above. may explain why many patients and some
functioning left ventricle. The circular motion of blood
in the abnormal apical segment max result in a more of the dogs did not show echocardiographic evidence
orderly and repetitive interaction of blood elements
than normally occurs, thereby enhancing the physical of blood stasis despite qualitativelv similar degrees of
alignment of potentially echogenic blood elements.
The persistence of blood in the dysfunctional apex. left ventricular dysfunction. Clinical two-dimensional
which could be deduced from the contrast injections.
echocardiographic imaging in adults is generally done
would augment this process.
with 3.0-3.5-MHz transducers. Higher frequency
We have not observed the echocardioTraphic pattern transducers might enhance the ultrasonic demonstra-
of blood stasis in patients in regions of the left ventricle tion of blood stasis. The echocardiographic patterns of
flow stasis in the dogs were more easily seen with a 5-
other than the apex (table Il. Nevertheless. with a MHz than with a 3-MHz transducer. In patients with
ventricular aneurysm of a nonapical wall. including apical wall motion abnormalities, a 5-MHz transducer
diastolic as well as systolic myocardial bulging. stasis can be used in the apical acoustic window because the
of blood should be severe and therefore potentiallx transducer is near the heart.. We have used this ap-
proach in patients to confirm the echo pattern of blood
echogenic. The apical segment of the ventricle, how- stasis when it was only suggested with a lower fre-
ever, may be uniquely predisposed to severe blood
stasis after ischemia, even in the absence of clear-cut quency transducer.
Our studies have several clinical imnplications. The
aneurysm. Left ventricular thrombi show a predilec-
detection of blood stasis at the apex mav identify pa-
tion for the cardiac apex,' and theoretical consider- tients at increased risk of developing left ventricular
ations indicate that the apex mav be particularlv sus- thrombus. Whether echocardiographic detection of re-
cional stasis without thrombosis should lead to a co)n
ceptible to increased wall stress and chances in

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ECHO DETECTION OF BLOOD STASIS/Mikell et al. 763

sideration of prophylactic anticoagulant therapy re- detecting left ventricular thrombus with two-dimensional echocar-
mains to be studied. In patients who have thrombi that diography. Emphasis on avoidance of false positive diagnoses. Am
disappear after anticoagulant therapy,'3 persistence of J Cardiol 47: 145, 1981
echocardiographic evidence of blood stasis might indi- 4. Asinger RW, Mikell FL. Elsperger J, Hodges M: Incidence of left
cate the need for long-term anticoagulant therapy. Our ventricular thrombosis after acute transmural myocardial infarc-
data do not allow us to draw conclusions on this possi- tion. Serial evaluation by two-dimensional echocardiography. N
bility. Further, blood stasis could be mistaken for Engl J Med 305: 297, 1981
thrombosis when the echo pattern is relatively intense. 5. MikeU FL, Asinger RW, Elsperger KJ, Anderson WR, Hodges M:
Failure to distinguish thrombosis from blood stasis Do the tissue acoustic properties of fresh left ventricular thrombi
could affect echocardiographic studies on the natural limit their visualization by two-dimensional echocardiography?
history or response to therapy of left ventricular Experimental observations. Am J Cardiol 49: 1157, 1982
thrombi. Careful real-time echocardiographic study of 6. Rourke T, Asinger RW, Mikell FL, Francis GS, Hodges M: Sector
the echoes after extrasystolic beats or hemodynamic echocardiographic technique: a systematic approach. Med Ultra-
interventions might be considered in uncertain cases. sound 3: 51, 1979
Finally, the ability to detect regional blood stasis in
vivo by echocardiography further demonstrates that 7. Solandt DY. Nassim R, Best CH: Production and prevention of
the acoustic impedance properties of early blood cardiac mural thrombosis in dogs. Lancet 2: 592, 1939
thrombosis can be detected ultrasonically.'
8. Meltzer RS, Tickner EG, Sahines TP, Popp RL: The source of
Acknowledgment ultrasound contrast effect. J Clin Ultrasound 8: 121, 1980

The authors thank Wendy Peek for preparation of the manuscript. 9. Hampton JR. Mitchell JRA: Thrombosis in human blood. In Co-
agulation, Haemostasis and Thrombosis, edited by Biggs R. Ox-
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Regional stasis of blood in the dysfunctional left ventricle: echocardiographic detection
and differentiation from early thrombosis.

F L Mikell, R W Asinger, K J Elsperger, W R Anderson and M Hodges

Circulation. 1982;66:755-763
doi: 10.1161/01.CIR.66.4.755

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